Blood Pressure, Cerebral Blood Flow, and Outcome in Stroke The impact of a lower admission blood pressure (BP) on outcome in acute ischemic stroke is well documented. In the International Stroke Trial (1ST), a retrospective analysis revealed that there was a 17.9% increase in the risk of early (2-week) death for every 10mmHg decrease in systolic blood pressure (SBP) under 150mmHg (International Stroke Trial Collaborative Group 1997, Leonardi-Bee 2002). Castro et al. found a Ushaped correlation between both systolic and diastolic blood pressure and mortality and infarct size in patients presenting with acute ischemic stroke, with low and very high blood pressures associated with worse outcome;the optimal systolic and diastolic pressures were around 180 and 100, respectively (Castro 2004). Similarly, a prospective study of 304 patients with first hemispheric ischemic stroke showed that the relative risk of death at 1 month rose 28.2% for every lOmmHg decrease in SBP below 130mmHg (Venmos 2004), and a retrospective study of 1,004 patients with ischemic stroke showed that patients with the lowest admission BP levels had significantly higher 30-day mortality than those with a SBP 150 to 169mmHg and diastolic blood pressure 100 to 109mmHg, leading to relative risks of 2.69 and 3.49 for lower SBP and diastolic blood pressure values, respectively (Okumura 2005). Other studies have found similar results (Castillo 2004, Yong 2005). There are theoretical reasons why a decrease in blood pressure can worsen injury in acute ischemic stroke. Astrup described the "ischemic penumbra," an area of at-risk brain surrounding a core of infarcted tissue that is electrically silent on electroencephalography but has intact ion pump function, and speculated that increasing perfusion to this area might lead to smaller eventual infarct size (Astrup 1981). In areas of acute ischemia, cerebral autoregulation is lost, and cerebral blood flow (CBF) is passively dependent on mean arterial pressure (MAP) (Eames 2002). A decreased MAP and decreased perfusion to this area might recruit more of the penumbra into the core of the stroke and worsen outcome. This leads to the question of whether increasing MAP will do the opposite. Patients with ischemic stroke have areas of non-infarcted tissue with low, pressure-dependent, passive CBF that can be augmented by increasing blood pressure (demonstrated on scintigraphy after an intracarotid injection of Xenon-133) (Olsen 1983). Animal studies of focal ischemia have shown that induced hypertension increases intraluminal hydrostatic pressure, opens up collaterals, increases perfusion to the penumbra, and reduces ischemic injury (Cole 1990). Meier et al. found that 37 patients with acute ischemic stroke who received multiple boluses of epinephrine to raise SBPs to the 210mmHg-220mmHg range had an increased 21-day survival when compared to 44 control patients (62.2% versus 36.4%, respectively;p = 0.02) (Meier 1991). Rordorf et al. used phenylephrine (a selective a-agonist) to elevate the blood pressures of 13 patients with acute ischemic stroke by 20%, to a target SBP between 160 mtnHg to 200 mmHg maximum within the first hour of presentation, and found that 7 of them had an improvement in NIHSS score of 2 or more (Rordorf 2001). Hillis described 6 patients with language deficits due to ischemic hypoperfusion (but hot infarction) of specific language centers in the brain who demonstrated marked improvement in language function when MAP was increased using induced hypertension with phenylephrine (Hillis 2001). He went on to perform a randomized trial with 15 ischemic stroke patients with greater than 20% diffusion-perfusion mismatch on MRI, and found that, at 3 days post-treatment, induced hypertension resulted in a significant acute improvements in NIHSS (sustained at 8 weeks), cognitive function, and volume of hypoperfused tissue on perfusion-weighted imaging (a decrease in the mean from 132 ml_ to 58 mL) (Hillis 2003). A large randomized, controlled trial investigating the use of BP manipulation in acute stroke has very recently finished enrollment, with results pending (Potter 2005).